Identification of the seven critical residues that control ZIKV-DENV cross-reactivity to engineer a non-cross-reactive ZIKV vaccine
Summary: The development of a Zika virus (ZIKV) vaccine is complicated by the high homology between ZIKV and dengue virus (DENV) envelope (E) proteins, resulting in immunological cross-reactivity that can exacerbate disease through antibody-dependent enhancement (ADE). Here, we screen 121 anti-DENV...
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| Language: | English |
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Elsevier
2025-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725008691 |
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| author | Ariadna Grinyo-Escuer Srikar Reddy Agnes L. Chenine J. Charles Whitbeck Sonya Jacobsen Allison Sheetz Kyle Doolan Diana M. Norden Nolan Frey Frederick W. Holtsberg M. Javad Aman Katja Fink Michael S. Diamond John S. Schieffelin James E. Crowe, Jr. Edgar Davidson Benjamin J. Doranz |
| author_facet | Ariadna Grinyo-Escuer Srikar Reddy Agnes L. Chenine J. Charles Whitbeck Sonya Jacobsen Allison Sheetz Kyle Doolan Diana M. Norden Nolan Frey Frederick W. Holtsberg M. Javad Aman Katja Fink Michael S. Diamond John S. Schieffelin James E. Crowe, Jr. Edgar Davidson Benjamin J. Doranz |
| author_sort | Ariadna Grinyo-Escuer |
| collection | DOAJ |
| description | Summary: The development of a Zika virus (ZIKV) vaccine is complicated by the high homology between ZIKV and dengue virus (DENV) envelope (E) proteins, resulting in immunological cross-reactivity that can exacerbate disease through antibody-dependent enhancement (ADE). Here, we screen 121 anti-DENV monoclonal antibodies (mAbs) for cross-reactivity with ZIKV E proteins. We identify 70 cross-reactive mAbs, 66 of which have epitopes that included at least one of seven E protein residues conserved among DENV1–DENV4 and ZIKV (R73, E79, W101, L107, F108, K110, and W212), establishing these residues as the key determinants of DENV-ZIKV cross-reactivity. Using these data, we engineer a ZIKV E protein variant with 10 mutations (“ZIKVm10”) that reduces cross-reactivity with DENV mAbs in vitro and minimizes the induction of anti-DENV antibodies in immunized mice. Passive serum transfer from ZIKVm10-immunized mice confers near-complete protection against lethal ZIKV challenge and reduced ADE for DENV infection, providing a pathway for improved ZIKV vaccine design. |
| format | Article |
| id | doaj-art-5c2bc3aa4dc044e6ba3cf04fdf8d203b |
| institution | Matheson Library |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-5c2bc3aa4dc044e6ba3cf04fdf8d203b2025-08-03T04:42:38ZengElsevierCell Reports2211-12472025-08-01448116098Identification of the seven critical residues that control ZIKV-DENV cross-reactivity to engineer a non-cross-reactive ZIKV vaccineAriadna Grinyo-Escuer0Srikar Reddy1Agnes L. Chenine2J. Charles Whitbeck3Sonya Jacobsen4Allison Sheetz5Kyle Doolan6Diana M. Norden7Nolan Frey8Frederick W. Holtsberg9M. Javad Aman10Katja Fink11Michael S. Diamond12John S. Schieffelin13James E. Crowe, Jr.14Edgar Davidson15Benjamin J. Doranz16Integral Molecular, Inc., Philadelphia, PA, USAIntegral Molecular, Inc., Philadelphia, PA, USAIBT Bioservices, Rockville, MD, USAIntegral Molecular, Inc., Philadelphia, PA, USAIntegral Molecular, Inc., Philadelphia, PA, USAIntegral Molecular, Inc., Philadelphia, PA, USAIntegral Molecular, Inc., Philadelphia, PA, USAIntegral Molecular, Inc., Philadelphia, PA, USAIntegral Molecular, Inc., Philadelphia, PA, USAIBT Bioservices, Rockville, MD, USAIBT Bioservices, Rockville, MD, USASingapore Immunology Network (SIgN), Agency for Science Technology and Research (A∗STAR), Singapore, SingaporeDepartments of Medicine, Molecular Microbiology, and Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USADepartment of Pediatrics, Section of Infectious Diseases, Tulane University School of Medicine, New Orleans, LA, USADepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USAIntegral Molecular, Inc., Philadelphia, PA, USAIntegral Molecular, Inc., Philadelphia, PA, USA; Corresponding authorSummary: The development of a Zika virus (ZIKV) vaccine is complicated by the high homology between ZIKV and dengue virus (DENV) envelope (E) proteins, resulting in immunological cross-reactivity that can exacerbate disease through antibody-dependent enhancement (ADE). Here, we screen 121 anti-DENV monoclonal antibodies (mAbs) for cross-reactivity with ZIKV E proteins. We identify 70 cross-reactive mAbs, 66 of which have epitopes that included at least one of seven E protein residues conserved among DENV1–DENV4 and ZIKV (R73, E79, W101, L107, F108, K110, and W212), establishing these residues as the key determinants of DENV-ZIKV cross-reactivity. Using these data, we engineer a ZIKV E protein variant with 10 mutations (“ZIKVm10”) that reduces cross-reactivity with DENV mAbs in vitro and minimizes the induction of anti-DENV antibodies in immunized mice. Passive serum transfer from ZIKVm10-immunized mice confers near-complete protection against lethal ZIKV challenge and reduced ADE for DENV infection, providing a pathway for improved ZIKV vaccine design.http://www.sciencedirect.com/science/article/pii/S2211124725008691CP: ImmunologyCP: Microbiology |
| spellingShingle | Ariadna Grinyo-Escuer Srikar Reddy Agnes L. Chenine J. Charles Whitbeck Sonya Jacobsen Allison Sheetz Kyle Doolan Diana M. Norden Nolan Frey Frederick W. Holtsberg M. Javad Aman Katja Fink Michael S. Diamond John S. Schieffelin James E. Crowe, Jr. Edgar Davidson Benjamin J. Doranz Identification of the seven critical residues that control ZIKV-DENV cross-reactivity to engineer a non-cross-reactive ZIKV vaccine Cell Reports CP: Immunology CP: Microbiology |
| title | Identification of the seven critical residues that control ZIKV-DENV cross-reactivity to engineer a non-cross-reactive ZIKV vaccine |
| title_full | Identification of the seven critical residues that control ZIKV-DENV cross-reactivity to engineer a non-cross-reactive ZIKV vaccine |
| title_fullStr | Identification of the seven critical residues that control ZIKV-DENV cross-reactivity to engineer a non-cross-reactive ZIKV vaccine |
| title_full_unstemmed | Identification of the seven critical residues that control ZIKV-DENV cross-reactivity to engineer a non-cross-reactive ZIKV vaccine |
| title_short | Identification of the seven critical residues that control ZIKV-DENV cross-reactivity to engineer a non-cross-reactive ZIKV vaccine |
| title_sort | identification of the seven critical residues that control zikv denv cross reactivity to engineer a non cross reactive zikv vaccine |
| topic | CP: Immunology CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725008691 |
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